# Assessing first-line treatment for advanced EGFR-mutated NSCLC in diverse clinicopathological subgroups: a systematic review and network meta-analysis

## TL;DR

This study identifies the best first-line treatments for advanced EGFR-mutated lung cancer based on patient characteristics like age and mutation type.

## Contribution

The study provides subgroup-specific treatment recommendations for EGFR-mutated NSCLC using network meta-analysis of diverse clinicopathological factors.

## Key findings

- Osimertinib plus chemotherapy improves progression-free survival across most patient subgroups.
- Amivantamab plus lazertinib offers the best overall survival outcomes in specific mutation and gender subgroups.
- Treatment combinations like afatinib plus cetuximab and dacomitinib show OS benefits in 19del and L858R mutation subgroups.

## Abstract

This network meta-analysis (NMA) aimed to indicate the most effective first-line therapeutic options for advanced EGFR-mutated NSCLC, particularly considering their specific clinicopathological characteristics.

Articles in the EMBASE, Cochrane Library, PubMed, and Web of Science databases and conference abstracts published as of December 2023, were searched to obtain data from randomized controlled trials (RCTs) of the first-line treatment of advanced EGFR-mutated NSCLC cases with EGFR-TKIs alone or together with other agents.

37 RCTs including 24 treatment regimens were incorporated into this NMA. With respect to the overall patient cohort, osimertinib + chemotherapy (CT) was associated with the greatest benefit to progression-free survival (PFS), whereas amivantamab + lazertinib yielded the greatest benefit to overall survival (OS). Osimertinib + CT yielded the best PFS outcomes irrespective of patient gender or EGFR mutation subtype. The combinations of amivantamab + lazertinib and icotinib + CT provided the best respective PFS outcomes in Asian and elderly patient cohorts. With respect to OS outcomes, afatinib + cetuximab provided the best outcomes for 19del and male cases, whereas dacomitinib provided the best OS for females and cases with L858R mutations. The respective gefitinib + CT and erlotinib + bevacizumab regimens were also associated with the greatest improvements in the OS of Asian and elderly cases.

This NMA revealed that cases with EGFR-mutated NSCLC may benefit from different first-line treatment regimens according to their clinicopathological characteristics. On the whole, osimertinib plus CT and amivantamab plus lazertinib emerged as the most noticeable treatment modalities for such cases. (PROSPERO ID: CRD42024506995)

The online version contains supplementary material available at 10.1186/s12885-025-15236-z.